Premium
Release by ultraviolet B (u.v.B) radiation of nitric oxide (NO) from human keratinocytes: a potential role for nitric oxide in erythema production
Author(s) -
Deliconstantinos George,
Villiotou Vassiliki,
Stravrides John C.
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb13341.x
Subject(s) - nitric oxide , keratinocyte , nitric oxide synthase , cytosol , erythema , human skin , tetrahydrobiopterin , chemistry , cyclase , calmodulin , biopterin , microbiology and biotechnology , biochemistry , in vitro , biology , enzyme , immunology , endocrinology , genetics
1 The mechanism of human sunburn is poorly understood but its characteristic features include the development of erythema. In this study we attempted to determine whether human keratinocytes possess a nitric oxide (NO) synthase (NOS), if this enzyme could be activated to release NO following exposure to ultraviolet B (u.v.B) and to define whether this photo‐induced response could be involved in the pathogenesis of sunburn erythema. 2 Treatment of human keratinocytes with various doses of u.v.B (290–320 nm) radiation (up to 100 mJ cm −2 ) resulted in a dose‐dependent release of NO and cyclic GMP production that was reduced by N G ‐monomethyl‐ l ‐arginine ( l ‐NMMA). 3 u.v.B irradiation of keratinocyte cytosol at varying doses (up to 50 mJ cm −2 ), resulted in a gradual rise in NO production, with a concomitant increase in soluble guanylate cyclase activity (sGC). 4 NOS isolated from the keratinocyte cytosol was constitutively expressed and was dependent on NADPH, Ca 2+ /calmodulin, tetrahydrobiopterin and flavins. 5 In reconstitution experiments, when purified NOS was added to purified sGC, both isolated from keratinocyte cytosol, a four fold increase in cyclic GMP was observed. The GMP was increased by NO synthesized following u.v.B radiation (up to 20 mJ cm −2 ) of NOS. 6 In in vivo experiments, guinea‐pigs were subjected to u.v.B light. A Protection Factor (PF) of 8.71 ± 2.85 was calculated when an emulsified cream formulation containing l ‐NMMA (2%) was applied to their skin. 7 The present results indicate that u.v.B radiation acts as a potent stimulator of NOS in keratinocytes. NO is lipophilic and may diffuse out of the keratinocytes, activating sGC in endothelial cells and neighbouring smooth muscle cells. This may be a major part of the integrated response of the skin leading to vasodilatation and erythema.